OBJECTIVE To provide reference for rational clinical use of immune checkpoint inhibitor （ICI）. METHODS Electronic medical record information of patients who received ICI treatment from January 1st 2020 to December 31st 2023 at a certain hospital was collected. Patients were divided into thyroid immune-related adverse event （irAE） group （subdivided into clinical hypothyroidism， clinical hyperthyroidism， subclinical hypothyroidism， and subclinical hyperthyroidism subgroups） and non- thyroid irAE group based on whether they experienced immune-induced thyroid irAE. Univariate and multivariate Logistic regression analyses were employed to analyze the influencing factors of ICI-related thyroid adverse events. RESULTS A total of 382 patients who received ICI treatment were included， with 137 cases in the thyroid irAE group （accounting for 35.9%） and 245 cases in the non-thyroid irAE group （accounting for 64.1%）. Multivariate Logistic regression analysis， following univariate screening， revealed that ICI combined with radiotherapy was positively associated with the occurrence of thyroid irAE [odds ratio （OR）＝2.157， 95% confidence interval （CI） （1.144， 4.066）， P＜0.05]， while lung squamous cell carcinoma was negatively associated with the occurrence of thyroid irAE [OR＝0.600， 95%CI （0.369， 0.975）， P＜0.05]. Among various thyroid irAE， nasopharyngeal malignancy was positively associated with the occurrence of immune-related clinical hyperthyroidism [OR＝4.678， 95%CI （1.149， 19.042）， P＜0.05]； ICI combined with radiotherapy [OR＝2.622， 95%CI （1.227， 5.603）， P＜0.05] and lung adenocarcinoma [OR＝2.013， 95%CI （1.078， 3.759）， P＜0.05] were positively associated with the occurrence of immune-related subclinical hyperthyroidism. Age was negatively associated with the occurrence of immune-related clinical hypothyroidism [OR＝0.944， 95%CI （0.896， 0.995）， P＜0.05]； age [OR＝0.963， 95%CI （0.932， 0.994）， P＜0.05] and ICI combined with chemotherapy [OR＝0.332， 95%CI （0.137， 0.802）， P＜0.05] were negatively associated with the occurrence of immune-related subclinical hypothyroidism. CONCLUSIONS Among patients receiving ICI treatment， younger patients are more prone to thyroid irAE. Patients receiving ICI combined with chemotherapy are less likely to experience subclinical hypothyroidism， while ICI combined with radiotherapy significantly increases the risk of thyroid adverse events.

OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of apixaban in the prevention and treatment of cancer-associated venous thromboembolism （CA-VTE）， and provide evidence-based reference for clinical treatment. METHODS Retrieved from PubMed， the Cochrane Library， CNKI， Wanfang， VIP database and other websites of health technology assessment （HTA）， systematic review/meta-analysis， pharmacoeconomic studies and HTA reports of apixaban in the prevention and treatment of CA-VTE were collected. After data extraction and quality evaluation， the results of the included study were analyzed descriptively. RESULTS A total of 23 literatures were included， involving 16 systematic review/meta-analysis and 7 pharmacoeconomic studies. In terms of efficacy， compared with placebo， prophylactic use of apixaban could significantly reduce the incidence of venous thromboembolism （VTE） in outpatient adult cancer patients receiving chemotherapy （P＜0.05）. Compared with low-molecular weight heparin （LMWH）， rivaroxaban and warfarin， there were no statistically significant differences in the incidence of VTE for apixaban （P＞0.05）； nevertheless， apixaban was ranked as the most preferable choice. For the treatment of patients with CA-VTE， compared with warfarin， apixaban could significantly reduce the recurrence rate of VTE （P＜0.05）. While compared with patients treated with LMWH， rivaroxaban， edoxaban and dabigatran， there were no statistically significant differences in the recurrence rates of VTE， deep venous thrombosis and pulmonary embolism among patients using apixaban （P＞0.05）. In terms of safety， compared with placebo， prophylactic use of apixaban showed a higher occurrence of major bleeding in outpatient adult cancer patients receiving chemotherapy （P＜0.05）， while compared withpatients treated with LMWH， rivaroxaban， and warfarin， there were no statistically significant differences in the incidence of major bleeding among patients using apixaban （P＞0.05）； despite this， apixaban was ranked as the most favorable option. For the treatment of patients with CA-VTE， compared with dalteparin， the incidence of major bleeding and all-cause mortality of apixaban were similar （P＞0.05）， while the incidence of clinically relevant non-major bleeding （CRNMB） was higher （P＜0.05）. Compared with edoxaban， the incidence of major bleeding of apixaban was reduced significantly （P＜0.05）， while there was no significant difference in the incidence of CRNMB， the incidence of clinically relevant bleeding and all-cause mortality （P＞0.05）. Compared with rivaroxaban， warfarin and dabigatran， there were no significant differences in the incidence of major bleeding， the incidence of CRNMB， the incidence of clinically relevant bleeding and all-cause mortality （P＞0.05）. In terms of cost-effectiveness， the researches in China showed that apixaban was cost-effective in preventing CA-VTE； foreign studies showed that apixaban was cost-effective in preventing and treating CA-VTE. CONCLUSIONS Apixaban is effective， safe and cost- effective in the prevention and treatment of CA-VTE.

The liver performs multiple life-sustaining functions. Hepatic diseases, including hepatitis, cirrhosis, and hepatoma, pose significant health and economic burdens globally. Along with the advances in nanotechnology, mesoporous silica nanoparticles (MSNs) exhibiting diversiform size and shape, distinct morphological properties, and favorable physico-chemical features have become an ideal choice for drug delivery systems and inspire alternative thinking for the management of hepatic diseases. Initially, we introduce the physiological structure of the liver and highlight its intrinsic cell types and correlative functions. Next, we detail the synthesis methods and physicochemical properties of MSNs and their capacity for controlled drug loading and release. Particularly, we discuss the interactions between liver and MSNs with respect to the passive targeting mechanisms of MSNs within the liver by adjusting their particle size, pore diameter, surface charge, hydrophobicity/hydrophilicity, and surface functionalization. Subsequently, we emphasize the role of MSNs in regulating liver pathophysiology, exploring their value in addressing liver pathological states, such as tumors and inflammation, combined with multi-functional designs and intelligent modes to enhance drug targeting and minimize side effects. Lastly, we put forward the problems, challenges, opportunities, as well as clinical translational issues faced by MSNs in the management of liver diseases.

Obesity, as a chronic recurrent disease, has become a major public health challenge in China. To implement the requirements of the Healthy China Initiative (2019—2030), under domestic guidelines or consensus statements on overweight and obesity, and in alignment with the latest scientific advances globally, the Quality control protocol for adult overweight and obesity screening in health management (examination) institutions (2025 edition) was developed. This protocol was drafted by the Health Management Center of Shanghai Changzheng Hospital and formulated through multiple rounds of deliberation by experts in China’s health examination quality control field. The protocol establishes unified standards for screening facilities, personnel qualifications, and measurement or testing procedures. It defines specific screening items, outlines a standardized screening pathway, and sets requirements for the final medical review, ensuring the scientific validity, effectiveness, and safety of the screening process. The implementation of this protocol will enhance the consistency of weight management practices for adults across health examination institutions and strengthen the quality control of overweight and obesity screening programs.

ObjectiveBased on non-targeted metabolomics， to analyze the regulation of endogenous differential metabolites in serum of type 2 diabetes mellitus（T2DM） rats by Fuling Yunhua granules， and to clarify the metabolic pathways through which this granules exerted its effect on improving T2DM. MethodSeventy SD rats， half male and half female， were randomly divided into the control group， model group， and high， medium， low dose groups of Fuling Yunhua granules（20.70， 10.35， 5.18 g·kg^-1 in raw drug amount） and the positive drug group（pioglitazone hydrochloride tablets， 8.1 mg·kg^-1）. Except for the control group， other groups were fed with high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin（STZ） to establish a T2DM rat model. After successful modeling， the treatment groups were administered the corresponding drugs by gavage， and the control group and model group were treated with an equal volume of saline by gavage， once/d， for 28 d. Fasting blood glucose（FBG） and glycosylated hemoglobin A1c（GHbA1c） levels were measured in all groups of rats during the administration period， and hematoxylin-eosin（HE） staining was used to observe the pathomorphological changes in the pancreatic tissues of rats at the end of the administration period. The endogenous metabolite levels in rat serum were detected by ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-LTQ-Orbitrap MS）， and the data were processed using principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. Differential metabolites were identified by the Human Metabolome Database（HMDB） and the Kyoto Encyclopedia of Genes and Genomes（KEGG）， and screened for differential metabolites with variable importance in the projection（VIP） value>1， P<0.05， and fold change（FC）<0.6 or FC>1. And the metabolic pathway enrichment analysis of the screened differential metabolites was performed by MetaboAnalyst 5.0， then the screened differential metabolites were diagnosed and evaluated by the receiver operating characteristic（ROC） curves. ResultCompared with the control group， the FBG level of rats in the model group increased significantly（P<0.01）， the GHbA1c content tended to increase， but the difference was not statistically significant， and the pancreatic tissue of rats was obviously damaged， the number of pancreatic islets decreased， and the pancreatic β-cells were obviously reduced， atrophied and enlarged. Compared with the model group， the FBG levels of rats in the high dose group of Fuling Yunhua granules and the positive drug group were significantly reduced after 2 weeks of administration（P<0.05， P<0.01）， the GHbA1c content of rats in the high dose group of Fuling Yunhua granules was significantly reduced（P<0.05）， and the pancreatic tissue lesions of rats in the different dose groups of Fuling Yunhua granules were reduced. The results of non-targeted metabolomics showed that 46 differential metabolites were significantly changed in the model group compared with the blank group. Pathway enrichment analysis found that T2DM mainly affected biological processes including biosynthesis of primary bile acid， D-amino acid metabolism， steroid hormone biosynthesis， and glycerophospholipid metabolism in rats. Compared with the model group， the levels of 8 differential metabolites in the high dose group of Fuling Yunhua granules were significantly adjusted， and the pathway enrichment analysis found that D-amino acid metabolism， retinol metabolism， glycine， serine and threonine metabolism， tryptophan metabolism and other metabolic pathways were mainly involved. ROC curves further analysis revealed that the four characteristic differential markers of 11-cis-retinol， D-piperidinic acid， D-serine， and p-cresol sulfate had high diagnostic value for the treatment of T2DM with Fuling Yunhua granules. ConclusionFuling Yunhua granules can improve the symptoms of T2DM rats by regulating the amino acid metabolic and retinol metabolic pathways through the modulation of endogenous differential metabolites.

The construction of regional medical centers is an important carrier for the country to further promote the reform of the new medical service system during the"14th Five-Year Plan"period.In view of the problems existing in the current construction of national regional medical centers,such as imperfect coordination mechanism,insufficient coordination power and lack of assessment and evaluation system,drawing on collaboration theory and case study method,the construction path of national regional medical centers was analyzed from three dimensions:management system collaboration,operation mechanism collaboration and evaluation mechanism collaboration;It explore and constructs the new management model of"13331"high quality development in National Regional Medical Centers;The results provide experience and case reference for promoting the high-quality development of national regional medical centers under the new situation in terms of party building leadership,medical technology,scientific and technological innovation,medical-education collaboration and brand influence.

Allergic rhinitis(AR) is an allergic inflammatory disease of the nasal mucosa in which the immune inflammatory response alters the local microenvironment of the nasal mucosa, causing mucus hypersecretion as one of the main pathological features of AR. Interleukin-13(IL-13) is the main inflammatory factor secreted by Th2 cells, it can be involved in AR mucus hypersecretion process by regulating Goblet cell proliferation and Mucin 5ac expression through various signaling pathways. Traditional Chinese medicine has obvious advantages in the treatment of AR and its mucus hypersecretion, while the IL-13-mediated signaling pathways are one of the important mechanisms in treating AR mucus hypersecretion. This article reviews the regulation of IL-13-mediated signaling pathways on AR mucus hypersecretion and the intervention effects of traditional Chinese medicine, which providing a theoretical basis for experimental research and new drug development in AR mucus hypersecretion.

BACKGROUND:Autoimmune regulator gene(Aire)and Wnt signaling pathway play an important role in the maintenance and differentiation of mouse embryonic stem cell pluripotency.However,whether the Wnt signal and Aire are involved in the differentiation of embryonic stem cells to thymic epithelial progenitor cells remains poorly understood. OBJECTIVE:To investigate the relationship of the Wnt signaling pathway and Aire with the differentiation of embryonic stem cells. METHODS:A two-step differentiation method was used to induce mouse embryonic stem cells to differentiate into endoderm and then into thymic epithelial progenitor cells.Mouse embryonic stem cells were infected with Aire shRNA lentivirus,and monoclonal stable strains were screened by puromycin.Mouse embryonic stem cells were collected on days 0,3 and 10 of the directed induction of differentiation after the induced differentiation by the two-step differentiation method.Cellular immunofluorescence,flow cytometry,western blot assay,and real-time qPCR were used to detect the expression changes of related genes and proteins. RESULTS AND CONCLUSION:(1)Immunofluorescence staining showed positive expression of SSEA1 and OCT4 on day 0 of targeted induction of differentiation.(2)Immunofluorescence staining showed double-positive expression of SOX17 and FOXA2 on day 3 of targeted induction of differentiation.(3)Flow cytometry results showed positive expression of EPCAM1,K5 and K8 on day 10 of targeted induction of differentiation.(4)Compared with undifferentiated mouse embryonic stem cells,the expressions of Wnt7a,β-catenin,and Gsk-3β proteins were elevated,and the expression level of Aire protein was decreased in induced differentiated thymic epithelial progenitor cells.(5)Compared with undifferentiated mouse embryonic stem cells,the expressions of Wnt7a,β-catenin,Gsk-3β and Aire mRNA were elevated in thymic epithelial progenitor cells.(6)Compared with normal cultured mouse embryonic stem cells and their ultimately differentiated thymic epithelial progenitor cells,the expression levels of Wnt7a,β-catenin and Gsk-3β proteins were reduced in mouse embryonic stem cells with knockdown of Aire genes and their final differentiated thymic epithelial progenitor cells.In conclusion,the Wnt signaling pathway and Aire are jointly involved in the process of targeted induction of differentiation of mouse embryonic stem cells into mouse thymic epithelial progenitor cells.

ObjectiveTo conduct a systematic review of the effect of active music therapy on cognitive function for older adults with cognitive impairment based on International Classification of Diseases, the 11th Revision (ICD-11), and International Classification of Functioning, Disability and Health (ICF). MethodsA PICO framework was constructed. Thematic keyword searches were conducted in databases including PubMed, Web of Science, Embase, CNKI, VIP, and Wanfang data, for literature on the effect of active music therapy on cognitive function for older adults with cognitive impairment, published up to November 5th, 2023. Information on authors, countries, publication date, sample characteristics, study designs, intervention methods, measurement tools and outcomes were extracted. The methodological quality of the researches was evaluated using the Physiotherapy Evidence Database (PEDro) scale. ResultsEight researches from six countries were included, which were all randomized controlled trials involving 356 older adults with mild cognitive impairment and dementia. The articles were published from 2014 to 2020, with an average of 7.4 of the PEDro scale. Active music therapy was used by singing and playing instruments. Interventions took place in hospitals, nursing homes, and health centers. The intervention duration ranged from mostly 30 to 60 minutes a time, with a few 120 minutes a time. Interventions were implemented mostly one to three times a week, lasting from eight to twelve weeks. Health outcomes focused on cognitive function, including overall cognitive function, executive function, attention function and memory function. ConclusionA theoretical framework for the benefits of active music therapy on the cognitive function for older adults with cognitive impairment has been constructed based on ICD-11 and ICF. Active music therapy can improve overall cognitive function, executive function, attention function and memory function for older adults with cognitive impairment.

ObjectiveTo conduct a systematic review of the health benefits of mindfulness interventions for older adults with insomnia disorders. MethodsThematic keyword search was conducted in databases including Web of Science, PubMed, Embase, EBSCO, CNKI, VIP and Wanfang data, for literature on the impact of mindfulness intervention on sleep quality in older adults with insomnia disorders, published up to August, 2023. The methodological quality of the researches was evaluated using the Physiotherapy Evidence Database (PEDro) scale. Insomnia disorders, sleep function and mindfulness interventions were coded using International Classification of Diseases 11th Revision, International Classification of Functioning, Disability and Health, and International Classification of Health Interventions Beta-3； and a systematic review was conducted following the PRISMA. ResultsNine researches from four countries were included, involving 800 participants, and all the researches were randomized controlled trials. The average score of PEDro scale was 7.1. The health-related conditions were insomnia disorders and insomnia disorders complicated with mild cognitive impairment. Mindfulness interventions used included mindfulness-based therapy for insomnia, mindfulness-based stress reduction, mindfulness-based cognitive therapy and mindfulness meditation. Interventions were implemented in institutions or health centers, care facilities, and community health service centers, varying from six to eight weeks. Health benefits of mindfulness intervention included improvements in sleep quality and psychological and behavioral health. ConclusionMindfulness interventions effectively improve sleep quality in older adults with insomnia disorders, alleviate negative emotional states such as depression, anxiety and perceived stress, and improve the quality of life.